172 results about "Caspase 3" patented technology

The present invention relates to methods and compositions for symptom-based differential diagnosis, prognosis, and determination of treatment regimens in subjects. In particular, the invention relates to the use of biomarkers, either individually or in combinations with one another to rule in or out diseases of the aorta and its branches, most particularly aortic aneurysm and / or aortic dissection, and for risk stratification in such conditions. Preferred markers include one or more of creatine kinase-BB (CK-BB), creatine kinase-MB (CK-MB), acidic calponin, basic calponin, B-type natriuretic peptide (BNP), NT-proBNP, proBNP, BNP79-108, BNP3-108, caldesmon, caspase-3, D-dimer, soluble elastin fragments, endothelial cell-selective adhesion molecule (ESAM), fibrillin-1, heart-type fatty acid binding protein, MMP-9, myeloperoxidase, myoglobin, smooth muscle myosin, smooth muscle myosin heavy chain, TIMP-1, free cardiac troponin I, complexed cardiac troponin I, free and complexed cardiac troponin I, free cardiac troponin T, complexed cardiac troponin T, and free and complexed cardiac troponin T, and preferred assays are configured to detect these markers.

A unique DHA product, 10, 17S-docosatriene (“Neuroprotectin D1” or “NPD1”), was found to provide surprisingly effective neuroprotection when administered right after an experimental stroke. Moreover, both nerve cells and retinal pigment epithelial (RPE) cells were found to synthesize 10,17S-docosatriene (NPD1) from DHA. NPD1 also potently counteracted H2O2 / TNFα oxidative stress-mediated cell apoptotic damage. Under the same oxidative-stress conditions, NPD1 up-regulated the anti-apoptotic Bcl-2 proteins, Bcl-2 and Bcl-xL, and decreased expression of the pro-apoptotic proteins, Bad and Bax. Moreover, in RPE cells NPD1 inhibited oxidative stress-induced caspase-3 activation, IL-1β-stimulated human COX-2 promoter expression, and apoptosis due to N-retinylidene-N-retinylethanolamine (A2E). Overall, NPD1 protected both nerve and retinal pigment epithelial cells from cellular apoptosis and damage due to oxidative stress. NPD1 concentration in the brain of Alzheimer's patients was found to be significantly decreased from that of controls. In cultured human brain cells, NPD1 synthesis was up-regulated by neuroprotective soluble β amyloid, and NPD1 was found to inhibit secretion of toxic β amyloid peptides.

Compounds and related methods for synthesis, and the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed in connection with modification of procaspases such as procaspase-3, and particular embodiments are capable of direct activation of procaspase-3 and procaspase-7 to the effector forms of caspase-3 and caspase-7. Procaspase-3 levels can vary among cancer cell types; several types have relatively high levels and can have increased susceptibility to chemotherapy by compounds and methods herein. Therapeutic applications are relevant for a variety of cancer conditions and cell types, e.g. breast, lung, brain, colon, renal, adrenal, melanoma, and others.

Activated protein C (APC), prodrug, and / or a variant thereof may be used as an inhibitor of apoptosis or cell death and / or a cell survival factor, especially for stressed or injured cells or tissues of the nervous system including subjects with neurode-generative disorders. Novel biological functions (e.g., neuroprotection) can be independent or separated from inhibition of clotting or inflammation, and other biological properties of APC (e.g., antithrombotic activity, ability to reduce NFκB-regulated gene expression). It can be used in the treatment of disease or other pathological conditions by at least inhibiting the p53-dependent and / or caspase-3-dependent pro-apoptotic signaling pathways in stressed or injured cells. Thus, APC, prodrugs, and variants thereof (e.g., APC protease domain mutants with reduced anti-coagulant activity) are prototypes of a class of agents for preventing apoptosis or cell death and / or promoting cell survival by direct action on brain cells. New protein C and / or APC variants with reduced anticoagulant activity may be selected thereby.

Inositol hexaphosphate (IP-6) is a polyphosphorylated carbohydrate with potent antioxidant activity to prevent active oxygen species-mediated mutagenesis, cell injury and carcinogenesis. IP-6 also activates DNA repair mechanisms. Sublethal radiation causes DNA damage through the formation of free radicals, reactive oxygen species, and pyrimidine crosslinks leading to cellular proliferation, cell cycle arrest and apoptosis. In the skin it results in the induction of skin cancer, premature skin aging, immuno-suppression, inflammation, and cell death. Likewise sublethal exposure to ionizing radiation as in nuclear blasts (war-time, accidental, terrorist-induced etc), cosmic radiation, etc. also causes the same spectrum of damage to the cells and the organisms with acute symptoms and eventual high risk of many cancers. IP-6 and / or inositol and their pharmaceutically acceptable salts and derivatives, including pyrophosphates and citrate derivatives, significantly counteract the harmful effects of radiation, affecting cell cycle progression in a protective manner (more cells in the protective GI phase) as well as decreasing apoptosis and caspase-3 activation. Various salts of IP-6 are used with comparable efficacy and the combination of IP-6+inositol affords the best protection against radiation-induced cell injury. Thus IP-6 and inositol are effective agents for protection against nuclear, solar and other radiation injuries.

The present invention relates to diagnostic imaging agents for in vivo imaging. The imaging agents comprise a synthetic caspase-3 inhibitor labelled with an imaging moiety suitable for diagnostic imaging in vivo. The invention also provides pharmaceutical and radiopharmaceutical compositions comprising the imaging agents, together with kits for the preparation of the radiopharmaceuticals. Also described are chelator conjugates of the caspase-3 inhibitor, which are suitable for the preparation of imaging agents comprising a radioactive or paramagnetic metal ion. The imaging agents are useful for the diagnostic imaging and or therapy monitoring in vivo of various disease states where caspase-3 is involved.

The invention relates to the use of at least one caspase inhibitor, in particular a caspase-3 inhibitor, for preparing a pharmaceutical composition for the prophylaxis and / or therapy of a viral infection, in particular an infection with an RNA negative-strand virus, preferably an influenza infection, and to a test system for identifying suitable active substances.

The present invention relates to a chimeric pro-caspase, which contains a pro-caspase domain and an oligomerizing domain. The invention also relates to an antibody that reacts specifically with a chimeric pro-caspase. In addition, the invention further relates to a polynucleotide encoding a chimeric pro-caspase, and to nucleotide sequences, which can hybridize specifically with a polynucleotide encoding a chimeric pro-caspase. The present invention also relates to a method of inducing apoptosis in a cell by providing a chimeric pro-caspase in the cell, wherein the chimeric pro-caspase includes a pro-caspase domain and an oligomerizing domain, whereby the chimeric pro-caspase forms an oligomer in the cell, thereby activating caspase activity of the chimeric pro-caspase and inducing apoptosis in the cell. The present invention further relates to a method of reducing the severity of a pathologic condition in a subject, by providing cells of the subject that are involved in the pathologic condition with a chimeric pro-caspase comprising a pro-caspase domain and an oligomerizing domain, whereby the chimeric pro-caspase forms an oligomer in the cells, thereby activating caspase activity of the chimeric pro-caspase, inducing apoptosis in the cells, and reducing the severity of the pathologic condition in the subject.

The invention provides an acetamide derivative with the structural formula as follows: R represents -X-Ar, -X-COOH, -CO-Ar, -SO2-Ar, -X-Het., or -X-NR1R2, wherein X represents alkylene with 1-8 carbon atoms and the alkylene is not substituted or is substituted by straight chain hydrocarbon or branched hydrocarbon with 1-5 carbon atoms; and Ar represents phenyl, pyridyl, naphthyl, pyrimidyl and quinolyl. The derivative can cause apoptosis by acting on Caspase-3 zymogen in cancer cells and can be widely applied in cancer treatment.

Methods and compositions are provided which inhibit the apoptotic activity associated with oxidative stress in many disease states. According to the invention, inhibition of chemical cleavage of PKCδ by caspase-3 results in reduction of apoptosis. Novel peptide inhibitors with the amino acid motif Asp Ile Pro Asp (SEQ ID NO:5) are also disclosed. The peptides are useful as inhibitors of PKCδ-mediated apoptosis and oxidative stress, and other diseases regulated by a catalytically active PKCδ.

The invention discloses N'-arylmethylene-2-(4-oxothiophene[2,3-d]pyrimidin-3-yl)acetyl hydrazone compounds, and a preparation method and application thereof. The structural general formula of the compounds is shown as a formula (I). Experimental results indicate that the compounds can induce cells to which Caspase-3 in human cervical carcinoma cells, human lung carcinoma cells and human breast carcinoma cells is dependent to die so as to inhibit the propagation of the carcinoma cells, also have low toxicity on normal cells, and can be used for preparing antitumor medicines for treating cervical carcinoma, lung cancer or breast cancer.

A method of detecting liver damage in a subject comprises measuring the level of caspase-3 generated cytokeratin-18 fragments in the bodily sample. The level of measuring the level of caspase-3 generated cytokeratin-18 fragments is then correlated with liver disease progression.

The invention discloses an enzyme-sensitive supramolecular hydrogel nano material which is easy to synthesize, a gelator and a preparation method of the gelator. The enzyme-sensitive supramolecular hydrogel nano material is characterized in that the gelator is synthesized by simple solid-phase polypeptide synthesis and conventional liquid-phase condensation reaction; gelatinization and gel dissolution are controlled in a manner of regulating pH; and meanwhile, the gelator comprises an oligopeptide sequence for identifying specificity of caspase 3, and thus, the gelator can be cut by the caspase 3 generated in the cell apoptosis process and survival time of cells can be prolonged. Compared with a conventional supramolecular hydrogel nano material, the enzyme-sensitive supramolecular hydrogel nano material disclosed by the invention has the advantages that complex reaction conditions are not required, the gelator is simple to synthesize and the gelatinization condition is easy to control; and the enzyme-sensitive supramolecular hydrogel nano material is sensitive to the specific caspase 3 generated in the cell apoptosis process, has excellent biocompatibility for cells and can be used for detecting activity of a specific enzyme related to apoptosis on the living cell plane and assisting cells to live in the cell culture.

Described here are novel, highly selective inhibitors and activity based probes (ABPs) for caspases 3, 7, 8, and 9 and legumain. The compounds selectively inhibit only certain caspases. A positional scanning combinatorial library (PSCL) approach was used to screen pools of peptide acyloxymethyl ketones (AOMKs) containing both natural and non-natural amino acids for activity against a number of purified recombinant caspases. These screens were used to identify structural elements at multiple positions on the peptide scaffold that could be modulated to control inhibitor specificity towards target caspases. Further disclosed are individual optimized covalent inhibitors that could also be equipped with various tags for use as activity based probes, as well as labeled substrates.

The invention relates to a cell apoptosis double-color detection and imaging probe and application thereof. The probe adopts a fluorescently-labeled cytochrome c nucleic acid aptamer and a caspase-3 substrate sequence polypeptide sequence as recognition elements and golden nanoparticles as a fluorescent energy receptor, response molecules are subjected to covalent modification on the surface of the receptor, and then fluorescence of two fluorescent dyes is quenched off in the energy transfer process simultaneously. When no target is available, the dye fluorescence is quenched off. When target molecules are available, the cytochrome c is combined with the aptamer, a substrate polypeptide of the cytochrome c is hydrolyzed with caspase-3, then the fluorescent dye is far away from the surfaces of golden nanoparticles, a fluorescence signal is generated, and detection and imaging of cytochrome c and caspase-3 are achieved. The probe provided by the invention is simple and convenient to synthesize, high in sensitivity and good in selectivity; two biomarkers related to cell apoptosis can be detected at the same time; and the probe is effectively applied to cell apoptosis imaging detection and cell apoptosis medicine evaluation.

The invention discloses application of chlorogenic acid in preparation of medicines for treating cardiomyopathy. The medicines have the effects of up-regulating myocardial specific expression structure genes ACTC1 and corresponding protein, down-regulating caspase-3 genes and corresponding protein thereof, and up-regulating Bc1-2 genes and corresponding protein. The invention also discloses a medicine for treating cardiomyopathy, and the medicine comprises chlorogenic acid and pharmaceutically acceptable auxiliary materials or auxiliary components. The invention also discloses a combined medicine for treating cardiomyopathy.

The invention discloses a caspase 3-sensitive fluorescence enhancement nano developer and a preparation method thereof. The preparation method is characterized by comprising the following steps: obtaining a connection having an appropriate length through simple solid-phase polypeptide synthesis; and obtaining the developer through conventional liquid-phase carboxylic acid / ammonia condensation reaction and fluorescent molecular marker reaction. Under physiologic conditions, the developer has favorable hydrophilicity and is easy to prepare; and meanwhile, the molecule of the fluorescence enhancement nano developer contains an oligopeptide sequence which can be specifically recognized by caspase 3, so that the oligopeptide sequence can be cut by the caspase 3 produced in the cell apoptosis process, thus indicating whether the cell enters an apoptosis state. Compared with the existing fluorescence enhancement apoptosis diagnosis kit, the preparation method disclosed by the invention is simple; the enzyme-sensitive fluorescence enhancement nano developer disclosed by the invention has favorable biocompatibility; the activity detection of a specific enzyme related to apoptosis can be completed in an in-vitro environment and a cell cracking solution through the detection of fluorescent signals; and the cell apoptosis state can be monitored on a living cell level.

To image apoptosis in vivo, small, membrane-permeable probes comprising a caspase 3 substrate, a fluorogenic dye and a radionuclide is provided. This dual-modality probe can be cleaved by caspase upon exposure to apoptotic cells, allowing imaging of caspase 3 and 7 activities using both optical and nuclear imaging techniques. The combined use of these methods provides the opportunity for a direct correlation between in vitro and in vivo biological activities and a viable method to treat disease

The invention discloses a procaspase-3 immunohistochemical diagnosis kit and a detection method thereof. The kit comprises an immunohistochemical staining agent, which comprises an initial antibody, a second antibody, enzyme, a substrate, a color-developing agent, a blocking agent and buffer solution, wherein the initial antibody is connected with tissue antigen; the second antibody is connected with the initial antibody; and the blocking agent is positioned at a non-specific binding site. The kit can measure expression level of the procaspase-3 antigen and cell position condition in the testee tissue accurately, provides guidance for clinical application of medicaments using the procaspase-3 protein as a target spot, and provides reference for clinical diagnosis of malignant tumor, hepatic fibrosis, renal injury and neurodegenerative lesion. The invention also discloses a control picture for detecting expression level of the procaspase-3 protein. The control picture is provided with a procaspase-3 high-expression control region, a procaspase-3 medium-expression control region, a procaspase-3 non-expression (low-expression) control region and a procaspase-3 detection region for placing the tissue to be detected. The control picture provides an accurate evaluation criterion for evaluation of the expression level of the procaspase-3.

The invention discloses a targeting gene-viro-therapy medicine specific for prostate cancer. An adenovirus is used, a natural promoter of an early gene EIA of the adenovirus is replaced by a promoter DD3 specific for the prostate cancer, and an oncolytic adenovirus is formed and carries anti-oncogene PTEN specific for the prostate cancer. If the anti-cancer effect of the anti-oncogene PTEN is not strong enough and is insufficient to completely kill the cancer, genes such as TRAIL, IL-24, MNSOD, CD, Smac, GM-CSF, IFN, IL-12, p53, RNAi, microRNA, Caspase 3 and Bax can added to the same carrier to be commonly used with the anti-oncogene PTEN, or two genes are linked to used through various schemes. The gene-viro-therapy medicine specific for the prostate cancer has high targeting treatment effect on the prostate cancer and basically has no influence on normal cells.

The invention discloses a specific gene-virus therapeutic drug for colorectal cancer. A natural promoter of an early gene E1A of an adenovirus is substituted by a colorectal cancer specific promoter CEA to form an oncolytic adenovirus carrying a specific antitumor gene ST13 of colorectal cancer. If the antitumor effect of the oncolytic adenovirus is not strong enough to kill all the cancer cells, the following genes may be added to a same vector with the oncolytic adenovirus for common usage: TRAIL, IL-24, MnSOD, CD, Smac, GM-CSF, IFN, IL-12, p53, RNAi, microRNA, Caspase 3 and Ba*; or two genes can be connected through various schemes. The gene-virus therapeutic drug for colorectal cancer provided by the invention has high therapeutic effect on targeting colorectal cancer, and has no effect on normal cells.

There is provided a hair tonic comprising at least two of an inhibitor against 5α reductase type 2, an inhibitor against transforming growth factor β2, and an inhibitor against caspase-3; a method comprising screening for at least two of inhibition against 5α reductase type 2, inhibition against transforming growth factor β2, and inhibition against caspase-3, or comprising screening for inhibition against caspase-3 and then for apoptosis inhibition, and a hair loss inhibitor having the effect of inhibiting caspase-3, and a hair loss inhibitor having the effect of inhibiting caspase-3 and of inhibiting apoptosis.

Single-domain anti-bodies that bind pro-apoptotic proteins Bax and caspase-3 are identified and isolated. These single-domain antibodies may be used to modulate the active of Bax and caspase-3, thereby modulating the symptoms and steps of oxidative stress and / or cell apoptosis, including Bax dimerization, mitochondrial permeabilization and the release of apoptotic proteins.

The invention relates to a shRNA (Short Hairpin Ribonucleic Acid) kit for treating an animal model suffered from an alzheimer disease. The kit internally comprises shRAN slow virus expression plasmid vector concentrated liquor capable of specifically suppressing a caspase-3 gene, and shRAN slow virus expression plasmid vector concentrated liquor as negative control, wherein the shRAN comprises sequences of SEQ ID No.1 and SEQ ID NO.2 in a sequence table. Compared with other means, the shRAN sequence or a reagent obtained therefrom can specifically and conveniently suppress the expression of disease-related proteins at high efficiency when entering the body of the animal model in a certain manner and lead disease-related genes to be silent, thereby achieving the treatment purpose; and therefore, the kit provided by the invention can be used for gene therapy for the animal model suffered from the alzheimer diseases.

The invention discloses a tumor radio sensitization medicine which has an active component of berberine. Proved by research: the berberine has the following efficacy of: 1, breast cancer cells are treated by berberine, which can induce dose-dependently G0 / G1 stage cell retardation and apoptosis; 2, the berberine remarkably reduces the expression level of cell cycle control associated protein cyclin B and apoptosis resisting protein Bcl-2 and increases the expression level of apoptins Bax and caspase-3; and 3, the breast cancer cells treated by the berberine remarkably improve the sensitiveness of the cells to radiotherapy. The tumor radio sensitization medicine can improve the treatment effect of tumor radiotherapy, lower the exposure dose of the radiotherapy of a tumor patient, and lower the toxic and side effects brought by the radiotherapy, thereby improving the living quality of patients.

The invention discloses application of rabdocetsin in preparing a product for inhibiting proliferation of esophageal squamous carcinoma cells. Proofed by experiment, the application has the advantages that the rabdocetsin can effectively inhibit the proliferation of the esophageal squamous carcinoma cells, the cloning formation of the esophageal squamous carcinoma cells, affecting the cycle progress of the esophageal squamous carcinoma cells, inducing the retardation of the cycle of the esophageal squamous carcinoma cells, inhibiting the DNA (deoxyribonucleic acid) restoration of the esophageal squamous carcinoma cells, inducing the withering of the esophageal squamous carcinoma cells, regulating up the expression amount of cleaved-caspase-9, regulating up the expression amount of cleaved-caspase-3, regulating up the expression amount of cleaved-PARP, inhibiting Akt signal pathways, inhibiting NF-kappa B signal pathways, and inhibiting the growth of tumors caused by the esophageal squamous carcinoma cells; the important application value is realized.

The invention is intended to develop a drug capable of directly or indirectly inhibiting the activation of caspase. Specifically, the invention provides a caspase 3 inhibitor comprising a protein comprising the same or substantially the same amino acid sequence as that represented by SEQ ID NO: 1, 2, 3 or 31 or a salt thereof. The protein of the invention, a partial peptide or a salt thereof is useful as a pharmaceutical such as a prophylactic and / or therapeutic agent for AIDS, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, pigmentary retinopathy, cerebellar degeneration, myelodysplastic syndrome, aplastic anemia, sideroblastic anemia, myocardial ischemia, conduction disturbance, chronic cardiac failure, graft-versus-host disease, or congenital or acquired enzymatic defect.

A method for preventing UV-induced skin-cellular injury by using a green algae extract and a cosmetic composition containing the green algae extract are disclosed. An effective dose of the green algae extract is used to protect fibroblasts from UV-induced apoptosis. The mechanism of the disclosed method is using the green algae extract to inhibit interaction between apoptosis pathway molecules Fas / FasL so as to inhibit an adapter protein (FADD) in a death-inducing signaling complex (DISC) and in turn to inhibit caspase-3 activation and cleaved polymerase (PARP) such that irreparable damage to DNA can be prevented. The green algae extract can be mixed with a skin permeable cosmetic composition so that the cosmetic composition possesses the function of preventing skin from UV-induced injury.

The invention belongs to the technical field of radiopharmaceuticals and nuclear medicine, in particular relates to an 18F-labeled polypeptide compound, and further discloses application thereof in preparation of a tumor apoptosis detection reagent. According to the 18F-labeled polypeptide compound 18F-AmBF3-GDEVD (probe 18F-1), high-yield and high-purity polypeptide is synthesized by using a solid-phase polypeptide synthesis method, an 18F-labeling group is introduced by 'click chemistry' to obtain a high-yield labeling precursor 1; a high-yield and high-purity PET probe 18F-1 is further successfully prepared by one-step 18F-labeling method. The whole reaction simplifies the step of 18F-labeling, the semi-preparation HPLC purification in a labeling process is avoided, and the labeling time is shortened. Meanwhile, the probe 18F-1 is displayed to be a potential targeted Caspase-3 apoptosis development probe, and has a good application prospect.

The invention discloses angstrom silver oral liquid and a preparation method and application in gastric cancer treatment thereof. The angstrom silver oral liquid is prepared from angstrom silver element powder, medicinal sugar and high-purity distilled water. The preparation method comprises the steps that the angstrom silver element powder is added to the high-purity distilled water to obtain anangstrom silver solution; dispersing treatment is conducted on the angstrom silver solution; the medicinal sugar is added to the dispersed angstrom silver solution, and dispersing treatment is conducted again; the dispersed angstrom silver solution is heated and sterilized, and the angstrom silver oral liquid is obtained after natural cooling is conducted. Angstrom silver injection has significantgastric cancer cell proliferation and migration inhibition capability. The appearance and weight of primary organs are not significantly changed after oral consecutive application of angstrom silveris conducted for 15 days, and H&E dyeing and immunohistochemical analysis prove that the expression amount of tissues structures and activated Caspase-3 of the primary organs after angstrom silver application is conducted is not significantly changed.